Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

Fujiwara, Hideaki; Maeda, Yoshinobu; Sando, Yasuhisa; Nakamura, Makoto; Tani, Katsuma; Ishikawa, Tadataka; Nishimori, Hisakazu; Matsuoka, Ken; Fujii, Nobuharu; Kondo, Eisei; Tanimoto, Mitsune

doi:10.1111/trf.13437

Cited by 28 publications

(20 citation statements)

References 39 publications

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“…1 but there are many significant severe complications. 2 Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication that occurs after HSCT 3 with a reported mortality rate ranging from 60% to 90%. 4 The clinical manifestations of TA-TMA include microvascular hemolytic anemia (MAHA), thrombocytopenia, microvascular thrombosis, and multiple organ failure, and the emblematic pathological manifestations include arteriole endothelium injury and intra-arteriole thrombosis.…”

Section: Introductionmentioning

confidence: 99%

von Willebrand Factor as a Predictor for Transplant-Associated Thrombotic Microangiopathy

Luo

Lai

et al. 2020

Clin Appl Thromb Hemost

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Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) is a severe complication associated with underlying endothelial damage. Secreted and released von Willebrand factor (vWF) correlates with endothelial cell injury, but its role in predicting prognosis for TA-TMA is unclear. In this prospective study, we evaluated the relationship between vWF and the incidence of TA-TMA after HSCT. A total of 79 consecutive patients undergoing HSCT from August 2016 to June 2018 were enrolled. Twenty-three (29%) patients met the established diagnostic criteria. Patients with TA-TMA had significantly higher nonrelapse mortality compared with those without TA-TMA (78.3% vs 8.9%; P < .001). Multivariable analysis demonstrated that vWF was a predictive biomarker for TA-TMA. The vWF value was higher for the TA-TMA group (mean ± standard deviation, 380.7% ± 78.8% vs 284.9% ± 104.5%; P < .001), and the area under the curve for vWF in the diagnosis of TA-TMA was 0.756. Furthermore, patients with ≥325% vWF had a higher 2-year cumulative hazard of TA-TMA (53.1% ± 8.2% vs 7.5% ± 4.2%; P < .001) and a lower 2-year survival (32.1% ± 9.1% vs 83.7% ± 6.2%; P < .001) compared with those with <325% vWF. Conclusion: von Willebrand factor is a useful predictor and prognostic measure for TA-TMA, which may help clinicians identify and manage this life-threatening disease earlier.

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Section: Introductionmentioning

confidence: 99%

von Willebrand Factor as a Predictor for Transplant-Associated Thrombotic Microangiopathy

Luo

Lai

et al. 2020

Clin Appl Thromb Hemost

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“…Recently, recombinant human soluble thrombomodulin has also been used successfully to treat thrombotic microangiopathy after hematopoietic stem cell transplantation. 22 Lastly, we need more studies to determine the exact pathophysiology of all these relatively uncommon disorders which can help proper diagnosis and management of these conditions especially in the setting of autologous stem cell transplants in hematological malignancies.…”

Section: Discussionmentioning

confidence: 99%

Enterococcus raffinosus Infection with Atypical Hemolytic Uremic Syndrome in a Multiple Myeloma Patient after Autologous Stem Cell Transplant

Mathur¹,

Hollowoa

Lala

et al. 2017

Hematology Reports

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Autologous hematopoietic stem cell transplant (AHSCT) is the standard of care in the treatment of multiple myeloma worldwide. Infections are one of the most common complications of the chemotherapy regimen and AHSCT. Thrombotic microangiopathies are one of the rare but potentially life-threatening complications of infections associated with AHSCT. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (HUS) are two most common type of thrombotic microangiopathies. The HUS is classically related to diarrheal illness such as with E.coli strain O157: H7 that produce Shiga-like toxins. But it has never been described with Enterococcus raffinosus urinary tract infections (UTI). Here we are describing a case of atypical HUS associated with Enterococcus raffinosus UTI in a patient with multiple myeloma after AHSCT. The management of atypical HUS especially after AHSCT is challenging. Eculizumab, a humanized monoclonal antibody against complement protein C5, and thrombomodulin have emerging role in the management of some cases, but more studies are needed to define evidence-based management of this condition.

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“…Once the cascade of TMA is triggered, nothing more than merely excluding suspected causes usually results in cure. (3) Most importantly, it is essential to detect TMA and to start the treatment at an early stage in order to reduce mortality. (1) Plasma exchange was spared as a last resort in this particular patient, considering the invasiveness and the possible adverse events of it in the early postoperative period.…”

Section: Discussionmentioning

confidence: 99%

“…2B [3]). (2,3) Thus, given the etiology of TMA and the functional mechanism of rTM, rTM can be of optimal use for the treatment of TMA after liver transplantation.…”

Section: Discussionmentioning

confidence: 99%

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Possible efficacy of recombinant human soluble thrombomodulin for the treatment of thrombotic microangiopathy after liver transplantation

et al. 2016

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Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

Abstract: This is the first report evaluating rTM administration for TA-TMA compared with previous treatments. Our data suggests that rTM might offer a better clinical outcome in patients with TA-TMA.

Cited by 28 publications

References 39 publications

von Willebrand Factor as a Predictor for Transplant-Associated Thrombotic Microangiopathy

von Willebrand Factor as a Predictor for Transplant-Associated Thrombotic Microangiopathy

Enterococcus raffinosus Infection with Atypical Hemolytic Uremic Syndrome in a Multiple Myeloma Patient after Autologous Stem Cell Transplant

Possible efficacy of recombinant human soluble thrombomodulin for the treatment of thrombotic microangiopathy after liver transplantation

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